Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Means with antiproliferative, immunomodulating (immunosuppressive) and anti-inflammatory action. The active leflunomide metabolite A771726 inhibits the enzyme dehydroorotate dehydrogenase and has an antiproliferative effect. A771726 in vitro inhibits mitogen-induced proliferation and synthesis of T-lymphocyte DNA.
The therapeutic effect of leflunomide was demonstrated in several experimental models of autoimmune diseases, including rheumatoid arthritis.
PHARMACOKINETICS
After oral administration, the absorption is 82-95%. Eating does not affect the absorption of leflunomide.
Leflunomide is rapidly metabolized in the intestinal wall and liver to one major (A771726) metabolite and several secondary metabolites, including 4-trifluoromethylalanine. Cmax of the metabolite A771726 is determined within 1-24 hours after the single dose taken. In plasma, A771726 binds rapidly to albumin. The unbound fraction of A771726 is 0.62%.
Biotransformation of leflunomide in A771726 and subsequent metabolism of A771726 itself are controlled by several enzymes and occur in microsomal and other cell fractions.
In plasma, urine and feces, traces of leflunomide are determined. Excretion of A771726 is slow and characterized by clearance of 31 ml / h. T 1/2 - about 2 weeks.
In patients on hemodialysis, excretion occurs faster and T 1/2 decreases.
INDICATIONS
Basic therapy of rheumatoid arthritis in order to reduce the symptoms of the disease and delay the development of structural damage to the joints.
Active form of psoriatic arthritis.
DOSING MODE
The initial dose is 100 mg daily for 3 days. The maintenance dose is 10-20 mg 1 time / day.
Therapeutic effect is manifested in 4-6 weeks from the beginning of admission and can increase for 4-6 months.
SIDE EFFECT
From the cardiovascular system: often - increased blood pressure.
On the part of the digestive system: often diarrhea, nausea, vomiting, anorexia, mucosal lesions of the oral cavity (aphthous stomatitis, ulceration of the lips), abdominal pain, elevation of liver enzymes (especially ALT, less often GGT, APF, bilirubin); rarely - hepatitis, jaundice, cholestasis; in some cases - liver failure, acute liver necrosis.
From the musculoskeletal system: often - tendovaginitis; possible - rupture of ligaments.
Dermatological reactions: often - hair loss, eczema, dry skin; possible - Stevens-Johnson syndrome, Lyell's syndrome, erythema multiforme.
On the part of the hematopoiesis system: often - leukopenia (leukocytes more than 2000 / Ојl); Possible - anemia, thrombocytopenia (platelets less than 100 000 / ОјL);rarely - eosinophilia, leukopenia (leukocytes less than 2000 / ОјL), pancytopenia; in some cases - agranulocytosis. The risk of developing hematological disorders increases with the recent, concomitant and subsequent use of myelotoxic drugs.
Allergic reactions: often - a rash (including maculopapular), itching; atypical - hives; in some cases - anaphylactic reactions.
On the part of the exchange processes: mild hyperlipidemia, hypophosphatemia, a decrease in the level of uric acid. Laboratory data (not clinically confirmed) indicate a slight increase in LDH, CK.
Other: in some cases - the development of severe infections and sepsis; possible development of rhinitis, bronchitis and pneumonia. With the use of immunosuppressive drugs, the risk of malignant and some lymphoproliferative processes increases. It is impossible to exclude the possibility of a reversible decrease in sperm concentration, the total number of spermatozoa and their mobility.
CONTRAINDICATIONS
Violations of liver function, severe immunodeficiency conditions (including AIDS); expressed violations of bone marrow hematopoiesis or anemia, leukopenia, thrombocytopenia due to other causes (except rheumatoid arthritis), severe infection, moderate or severe renal insufficiency (due to insignificant experience of clinical observations), severe hypoproteinemia (including nephrotic syndrome ), pregnancy, lactation, children and adolescents under 18, hypersensitivity to leflunomide.
PREGNANCY AND LACTATION
Contraindicated in pregnancy, during lactation.
Contraindicated in women of childbearing age who do not use adequate contraception.
Men receiving leflunomide treatment should be warned about a possible fetotoxic effect and the need to use adequate contraception.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated with moderate or severe renal failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in the violation of liver function.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
SPECIAL INSTRUCTIONS
The application is possible only after a thorough medical examination of the patient.
Before starting treatment, one should keep in mind the possibility of increasing the number of side effects in patients who have previously received other basic agents for the treatment of rheumatoid arthritis, which have hepato- and hematotoxic effects.
The active metabolite leflunomide A771726 is characterized by a long T 1/2 . Therefore, side effects can occur even after the cessation of leflunomide treatment. In case of such cases of toxicity or when switching to another basic preparation after treatment with leflunomide, a procedure for "laundering" should be followed (after stopping treatment with leflunomide, colestramine is given at a dose of 8 g 3 times / day for 11 days or 50 g of activated charcoal powdered into powder , 4 times / day for 11 days).
It should be borne in mind that with the development of severe dermatological adverse reactions, severe infections, leflunomide should be discontinued and immediately begin the procedure for "laundering".
It is necessary to observe patients with tuberculin reactivity because of the risk of activation of tuberculosis.
Given the long T 1/2 leflunomide, during the period of treatment it is not recommended to vaccinate with live vaccines.
DRUG INTERACTION
Increased adverse reactions may occur in the case of recent or concomitant use of hepatotoxic or hematotoxic drugs, or when the administration of these drugs begins after treatment with leflunomide without the procedure for "laundering".
In vitro studies have shown that the leflunomide metabolite A771726 inhibits the activity of the CYP2C9 isoenzyme. When used simultaneously with drugs metabolized by this enzyme system (phenytoin, warfarin, tolbutamide), one can not exclude the development of undesirable effects of drug interaction.
